This proposal is for the study of two aspects of cerebral cortical development. The first addresses the question whether all cortical efferent project systems are initially widely distributed and only at some later stage become restricted in their distribution, either through neuronal death or the selective elimination of certain, early-formed, axon collaterals. The second concerns the issue whether or not, in complexd neuronal structures such as the mammalian cerebral cortex there is a naturally-occuring cell death during development which removes a significant fraction of the initially formed neurons, as has been found in several subcortical neuronal populations especially in non-mammalian vertebrates. It has recently been shown that early in postnatal life the neurons that give rise to callosal projections are widely distributed, but during the subsequent several weeks this distribution becomes restricted to certain cytoarchitectonically or functionally defined regions. Using two retrogradely transported dyes, my colleagues and I have shown that, in the rat parietal cortex, this restriction is brought about principally (if not exclusively) by the selective loss of callosal collaterals by a significant number of the early callosally-projecting neurons. I am now proposing to examine other cortico-cortical and cortico-fugal projections in the same way, by retrogradely labeling the neurons in the first two or three days after birth with one dye, true blue, and some three weeks later with a second, clearly distinguishable dye, nuclear yellow. These experiments should establish: (a) if there is a progressive restriction in the various cortical projection systems, and (b) if there is, when the restriction occurs and whethe it too is brought about by the loss of collaterals or by the death of some proportion of the relevant neurons. Other dye experiments will attempt to establish where the neurons that transiently project to the opposite hemisphere send their axons and to what extent the transient callosal projection provides for plasticity in the callosal system. To determine whether or not cell death is an important factor in the development of the cerebral cortex, I propose to carry out a quantitative analysis of the number of neurons in the cerebral cortex of adult rats and of rats at various stages during the first three weeks of their postnatal life.